Increased Doses of Vaginal Progesterone for the Prevention of Preterm Birth in Twin Pregnancies: A Randomised Controlled Double-Blind Multicentre Trial

BJOG. 2013 Jan;120(1):50-7. doi: 10.1111/j.1471-0528.2012.03448.x. Epub 2012 Aug 13.

Abstract

Objective: Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90-200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies.

Design: Randomised controlled double-blind multicentre trial (1:1:1).

Setting: The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain).

Population: Women with dichorionic diamniotic twin pregnancies.

Methods: The women self-inserted two vaginal pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n = 97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention-to-treat basis.

Main outcome measure: Preterm birth rate.

Results: The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone-treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200- versus 400-mg progesterone groups. No serious adverse effects were encountered.

Conclusions: Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400-mg progesterone dose offered no advantages over the 200-mg regimen.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravaginal
  • Adult
  • Birth Weight
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Medication Adherence
  • Pessaries
  • Pregnancy
  • Pregnancy Outcome
  • Pregnancy, Twin*
  • Premature Birth / prevention & control*
  • Progesterone / administration & dosage*
  • Progestins / administration & dosage*
  • Self Care

Substances

  • Progestins
  • Progesterone